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OLFACTORY TOXICITY OF B,B'-IMINODIPROPIONITRILE (IDPN) IN THE RAT
Citation:
Clair, M., J. Llorens, J. O'Callaghan, D. Peele, AND K. Crofton. OLFACTORY TOXICITY OF B,B'-IMINODIPROPIONITRILE (IDPN) IN THE RAT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/097 (NTIS PB93175669).
Description:
Following a pilot study which revealed olfactory epithelial degeneration induced by iminodipropionitrile (IDPN), dose-response and time course analyses were undertaken to further characterize the effects of IDPN on the olfactory system. Male Long-Evans rats received 25-400 mg/kg IDPN i.p. and were sacrificed 24 hr later. A second group received 400 mg/kg IDPN i.p. and were sacrificed 24 hr after a single dose, 24 hr after 2 daily doses, and 1, 3, 7, 14, 28, and 56 days after 3 consecutive daily doses. Formalin-fixed nasal cavities were decalcified and embedded in paraffin; 5 um sections were stained with H&E, an antibody to the middle neurofilament protein, or antiserum to olfactory marker protein. Olfactory bulbs were removed for slot-blot analyses of glial fibrillary acidic protein (GFAP), synapsin I, and p38. A third group was treated with saline or IDPN as described above and perfused with paraformaldehyde 6 hr or 1, 2, 3, 7, 14, or 28 days after the last dose; olfactory bulbs were stained using a modified Gallyas technique to localize degenerating axons. Twenty-four hrs after a single treatment with 200 or 400 mg/kg, there was severe and high site-specific olfactory mucosal degeneration in the dorsal-medial nasal cavity; olfactory mucosal regeneration was incomplete 8 wk later. Neurofilament-filled axonal swellings were not present. Olfactory bulb GFAP increased after IDPN treatment, peaking 7 days after three daily 400 mg/kg doses, and remaining significantly elevated.